Book Review

Ethical Issues in Drug Testing, Approval, and Pricing: The clot-dissolving drugs

N Engl J Med 1996; 334:126-127January 11, 1996

Article

Ethical Issues in Drug Testing, Approval, and Pricing: The clot-dissolving drugs
By Baruch A. Brody. 268 pp. New York, Oxford University Press, 1995. $35. ISBN: 0-19-508831-X

In July 1995, the U.S. Department of Energy published and posted on the Internet a list of human radiation experiments involving the department or its predecessors. This list was followed in October by the final report of the Advisory Committee on Human Radiation Experiments. The list of experiments and the final report (the result of the advisory committee's careful reconstruction of these radiation experiments) attest to the Department of Energy's recent “openness initiative” regarding its past and present activities, particularly department-supported research that involved the participation (and misuse through excessive exposure) of a number of human subjects in some 425 ionizing-radiation experiments conducted from the early 1940s through the early 1970s.

On September 21, 1995, the Food and Drug Administration (FDA) proposed new rules for the protection of human subjects — particularly those who could “feasibly” participate in biomedical research in the emergency room setting. These rules would go into effect “prior to initiation of an experimental treatment” and would provide a “narrow exception” serving to amend the FDA's present regulations concerning informed consent. The new regulations are designed “to reduce confusion as to when such research can proceed without obtaining informed consent” — that is, when consent that cannot be obtained by the usual procedures with competent persons, including so-called vulnerable subjects at low risk, can be waived (by the institutional review board, not the subjects), since consent cannot be deferred even under the proposed rules.

Baruch A. Brody (Leon Jaworski Professor of Biomedical Ethics at Baylor College of Medicine) has carefully crafted the four chapters that constitute Ethical Issues in Drug Testing, Approval, and Pricing. It appears at a most propitious moment, not only because of the FDA's controversial proposed rules and the Department of Energy's historical moral excursus, but because after the publication of the standard regulations of the National Institutes of Health (NIH) in 1974 and its Belmont Conference in 1976 (and report of 1979), the vast majority of institutional review board members — whose general task has been and remains the review of scientific protocols that necessitate the participation of human subjects — may well have concluded prematurely that research ethics had actually come to an end. Just consider the five points underscored by Brody: apply the principle of equity when selecting research subjects; be certain to ensure subjects' confidentiality; be certain also to apply the principle of independently assessed benefits and risks; be sure that each subject has been adequately informed and understands what has been said so that she or he can provide informed consent; and be certain the consent form is lucidly written, truly informative, and signed. For Brody, who says he is simply “telling a story” (not one for casual reading, be assured), it only begins here.

Brody poses a general question: Whatever happened to research ethics? His general answer is that important bioethical issues have not been adequately addressed, either in the literature or in the detailed FDA and NIH regulations. His particular questions and analyses are couched in a carefully documented account of one research enterprise that culminates in the pricing and marketing of clot-dissolving drugs. For Brody, this is the “case,” giving the term a denotation other than the casuistic analysis of a particular patient's multiple problems that may or may not involve bioethical dilemmas. Indeed, Brody critically analyzes a number of concepts at work in particular research contexts: the busy emergency room, where he focuses on the limits and ethically licit criteria that ought to be imposed when obtaining informed consent for participation in research trials from patients in life-threatening situations; the placebo-controlled trial and the scientific and moral criteria that warrant its use or avoidance for specifically circumscribed protocols; and the danger posed for the community of investigators should any of them give even the appearance of impropriety, acting so as to suggest a conflict of interest.

Brody not only addresses the troubling ethical issues that emerge in the process of drug approval and adoption (discussing in some detail the regulatory schemes of the NIH and those in the United Kingdom, including the relevance of the NIH regulations for the AIDS crisis), but also offers his readers a novel proposal for a morally licit, “society-wide drug regulation scheme” that would protect the vulnerable and the rest of us as well.

He closes the book with a detailed critique of the “classic” position (“the physician must always emphasize the clinical benefits to the patient regardless of the costs”) and takes into account the fact that, especially today, limitations on interventions for economic reasons are inevitable. In the end, Brody defends the position that “physicians should consider costs in making clinical decisions.”

Brody, careful throughout to avoid unnecessary diversions and wordiness, does not use (as the emperor said to Mozart in the film Amadeus) “too many notes.” Indeed, it is unfortunate that the title does not reflect the full range of concepts that this remarkably readable book addresses. In earlier centuries, it might well have been called Ethical, Political, legal, and Health Policy Issues in Drug Development, Testing, Approval, Patenting, Adoption, and Pricing. A work addressing all these issues in one book is a tour de force.

Brody's book should be required reading for researchers who have requested or who intend to solicit the participation of human subjects in biomedical or behavioral research, for members of institutional review boards whose task is to review the protocols of their peers, and for policy analysts concerned with drug approval and pricing. As Brody repeatedly reminds us, “The issues are far from academic.” Innumerable lives have been and will remain in the balance.

Stuart F. Spicker, Ph.D.
University of New Mexico School of Medicine, Albuquerque, NM 87131